Clinical diabetic cardiomyopathy: A two-faced disease with restrictive and dilated phenotypes

European Heart Journal

Volumn 36, Issue 27, 2015, Pages 1718-1727

  Seferović, Petar M ^a   Paulus, Walter J ^b  

^a University Medical Center   (Serbia)

^b VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Diabetes mellitus; Diabetic cardiomyopathy; Diastolic dysfunction; Heart failure; Left ventricular Remodelling

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ADVANCED GLYCATION END PRODUCT; ANGIOTENSIN RECEPTOR ANTAGONIST; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIPEPTIDYL PEPTIDASE IV INHIBITOR; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; GLUCOSE; INSULIN; METFORMIN; MINERALOCORTICOID ANTAGONIST; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; SPIRONOLACTONE; SULFONYLUREA DERIVATIVE; ANTIDIABETIC AGENT;

AUTOIMMUNITY; CELL DEATH; DIABETIC CARDIOMYOPATHY; DIAGNOSTIC PROCEDURE; ENDOTHELIAL DYSFUNCTION; GLUCOSE METABOLISM; HEART FAILURE; HEART FAILURE WITH PRESERVED EJECTION FRACTION; HEART LEFT VENTRICLE FAILURE; HEART MUSCLE CELL; HEART MUSCLE PERFUSION; HEART VENTRICLE REMODELING; HUMAN; HYPERGLYCEMIA; INSULIN RESISTANCE; LIFESTYLE MODIFICATION; LIPOTOXICITY; MICROVASCULATURE; PATHOPHYSIOLOGY; PHENOTYPE; PREVALENCE; PRIORITY JOURNAL; REDUCED LEFT VENTRICULAR EJECTION FRACTION; REVIEW; TREATMENT INDICATION; VASCULITIS; CARDIOMYOPATHY, DILATED; CARDIOMYOPATHY, RESTRICTIVE; DIABETIC CARDIOMYOPATHIES; HEART VENTRICLE FUNCTION; METABOLISM; PHYSIOLOGY; RISK REDUCTION;

AUTOIMMUNITY; CARDIOMYOPATHY, DILATED; CARDIOMYOPATHY, RESTRICTIVE; DIABETIC CARDIOMYOPATHIES; GLYCOSYLATION END PRODUCTS, ADVANCED; HEART FAILURE; HUMANS; HYPERGLYCEMIA; HYPOGLYCEMIC AGENTS; INSULIN RESISTANCE; PHENOTYPE; RISK REDUCTION BEHAVIOR; VENTRICULAR DYSFUNCTION;

EID: 84937227669     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/ehv134     Document Type: Review

References (123)

1. Lundbaek K. Diabetic angiopathy. A specific vascular disease. Lancet 1954;263: 377-379.
2. Lundbaek K. Is there a diabetic cardiopathy? In: Schettler G. (ed.), "Pathogenetische faktoren des myokardinfarkts". Schattauer, Stuttgart, 1969, 63-71.
3. Rubler S, DlugashJ, Yuceoglu YZ, KumralT, BranwoodAW, Grishman A. Newtype of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol 1972; 30:595-602.
4. Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, Dubourg O, Kühl U, Maisch B, McKenna WJ, Monserrat L, Pankuweit S, Rapezzi C, Seferovic P, Tavazzi L, Keren A. Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2008;29:270-276.
5. rd ed. Philadelpia, Mosby-Elsevier, 2010; 1107-1109.
6. Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev 2013;93: 137-188.
7. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. NEnglJ Med 2006;355:251-259.
8. European Study Group on Diastolic Heart Failure. How to diagnose diastolic heart failure. Eur Heart J 1998;19:990-1003.
9. Paulus WJ, Tschöpe C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbély A, Edes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J 2007;28:2539-2550.
10. McMurray J, Pfeffer MA. New therapeutic options in congestiveheart failure. Part II. Circulation 2002;105:2223-2228.
11. Fang ZY, Prins JB, Marwick TH. Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications. Endocrine Rev 2004;25:543-567.
12. Maisch B, Alter P, Pankuweit S. Diabetic cardiomyopathy - fact or fiction? Herz 2011;36:102-115.
13. Dunlay SM, Roger VL, Weston SA, Jiang R, Redfield MM. Longitudinal changes in ejection fraction in heart failure patients with preserved and reduced ejection fraction. Circ Heart Fail 2012;5:720-726.
14. Cheng S, Xanthakis V, Sullivan LM, Lieb W, Massaro J, Aragam J, Benjamin EJ, Vasan RS. Correlates of echocardiographic indices of cardiac remodeling over the adult life course: longitudinal observations from the Framingham Heart Study. Circulation 2010;122:570-578.
15. Lam CS, Roger VL, Rodeheffer RJ, Bursi F, Borlaug BA, Ommen SR, Kass DA, Redfield MM. Cardiac structure and ventricular-vascular function in persons with heart failure and preserved ejection fraction from Olmsted County. Circulation 2007;115:1982-1990.
16. Paulus WJ, Tschoepe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol 2013;62:263-271.
17. Paulus WJ, v Ballegoij JJM. Treatment of heart failure with normal ejection fraction. An inconvenient truth!. J Am Coll Cardiol 2010;55:526-537.
18. Bertoni AG, Tsai A, Kasper EK, Brancati FL. Diabetes and idiopathic cardiomyopathy. A nationwide case-control study. Diabetes Care 2003;26:2791-2795.
19. Van Heerebeek L, Hamdani N, Handoko L, Falcao-Pires I, Musters RJ, Kupreishvili K, Ijsselmuiden AJJ, Schalkwijk CG, Bronzwaer JGF, Diamant M, Borbely A, van der Velden J, Stienen GJM, Laarman GJ, Niessen HWM, Paulus WJ. Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation endproducts and myocyte resting tension. Circulation 2008;117:43-51.
20. Lindman BR, Dávila-Román VG, Mann DL, McNulty S, Semigran MJ, Lewis GD, de Las Fuentes L, Joseph SM, Vader J, Hernandez AF, Redfield MM. Cardiovascular phenotype in HFpEF patients with or without diabetes: A RELAX trial ancillary study. J Am Coll Cardiol 2014;64:541-549.
21. Kamalesh M, Nair G. Disproportionate increase in prevalence of diabetes among patients with congestive heart failure due to systolic dysfunction. Int J Cardiol 2005;99:125-127.
22. Bertoni AG, Hundley WG, Massing MW, Bonds DE, Burke GL, Goff DC Jr. Heart failure prevalence, incidence and mortality in the elderly with diabetes. Diabetes Care 2004;27:699-703.
23. MurciaAM, HennekensCH, Lamas GA, Jimenez-NavarroM, RouleauJL, FlakerGC, Goldman S, Skali H, Braunwald E, Pfeffer MA. Impact of diabetes on mortality in patients with myocardial infarction and left ventricular dysfunction. Arch Intern Med 2004;164:2273-2279.
24. Held C, Gerstein HC, Yusuf S, Zhao F, Hilbrich L, Anderson C, Sleight P, Teo K, for the ONTARGET/TRANSCEND investigators. Glucose levels predict hospitalization for congestive heart failure in patients at high cardiovascular risk. Circulation 2007;115:1371-1375.
25. MacDonald MR, Jhund PS, Petrie MC, LewseyJD, Hawkins NM, Bhagra S, Munoz N, Varyani F, Redpath A, Chalmers J, MacIntyre K, McMurray JJ. Discordant short- and long-term outcomes associated with diabetes in patients with heart failure: importance of age and sex: a population study of 5.1 million people in Scotland. Circ Heart Fail 2008;1:234-241.
26. MacDonald MR, Petrie MC, Varyani F, Ostergren J, Michelson EL, Young JB, Solomon SD, Granger CB, Swedberg K, Yusuf S, Pfeffer MA, McMurray JJ, CHARM Investigators. Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur Heart J 2008;29:1377-1385.
27. Dei Cas A, Spigoni V, Ridolfi V, Metra M. Diabetes and chronic heart failure: from diabetic cardiomyopathy to therapeutic approach. Endocr Metab Immune Disord Drug Targets 2013;13:38-50.
28. Iribarren C, Karter AJ, Go AS, Ferrara A, Liu JY, Sidney S, Selby JV. Glycemic control and heart failure among adult patients with diabetes. Circulation 2001;103: 2668-2673.
29. McMurray JJ, Gerstein HC, Holman RR, Pfeffer MA. Heart failure: a cardiovascular outcome in diabetes that can no longer be ignored. Lancet Diabetes Endocrinol 2014; 2:843-851.
30. van Heerebeek L, Borbely A, Niessen HW, Bronzwaer JGF, van der Velden J, Stienen GJ, Linke WA, Laarman GJ, Paulus WJ. Myocardial structure and function differ in systolic and diastolic heart failure. Circulation 2006;113:1966-1973.
31. Poornima IG, Parikh P, Shannon RP. Diabetic cardiomyopathy: the search for a unifying hypothesis. Circ Res 2006;98:596-605.
32. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000;404:787-790.
33. Shenouda SM, Widlansky ME, Chen K, Xu G, Holbrook M, Tabit CE, Hamburg NM, Frame AA, Caiano TL, Kluge MA, Duess MA, Levit A, Kim B, Hartman ML, Joseph L, Shirihai OS, Vita JA. Altered mitochondrial dynamics contributes to endothelial dysfunction in diabetes mellitus. Circulation 2011;124:444-453.
34. TangX, Luo YX, Chen HZ, Liu DP. Mitochondria, endothelial cell function, and vascular diseases. Front Physiol 2014;5:175.
35. van Heerebeek L, Hamdani N, Falcao-Pires I, Leite-Moreira AF, Begieneman MP, Bronzwaer JG, van der Velden J, Stienen GJ, Laarman GJ, Somsen A, Verheugt FW, Niessen HW, Paulus WJ. Low myocardial protein kinase G activity in heart failure with preserved ejection fraction. Circulation 2012;126:830-839.
36. Hamdani N, Bishu KG, Frieling-Salewsky M, Redfield MM, Linke WA. Deranged myofilament phosphorylation and function in experimental heart failure with preserved ejection fraction. Cardiovasc Res 2013;97:464-471.
37. Hamdani N, Franssen C, Lourenço A, Falcão-Pires I, Fontoura D, Leite S, Plettig L, López B, Ottenheijm CA, Becher PM, González A, Tschöpe C, Díez J, Linke WA, Leite-Moreira AF, Paulus WJ. Myocardial titin hypophosphorylation importantly contributes to heart failure with preserved ejection fraction in a rat metabolic risk model. Circ Heart Fail 2013;6:1239-1249.
38. Falcao-Pires I, Hamdani N, Borbely A, Gavina C, Schalkwijk CG, van der Velden J, van Heerebeek L, Stienen GJM, Niessen HWM, Leite-Moreira AF, Paulus WJ. Diabetes worsens diastolic left ventricular dysfunction in aortic stenosis through altered myocardial structure and cardiomyocyte stiffness. Circulation 2011;124: 1151-1159.
39. Montaigne D, Marechal X, Coisne A, Debry N, Modine T, Fayad G, Potelle C, El Arid JM, Mouton S, Sebti Y, Duez H, Preau S, Remy-Jouet I, Zerimech F, Koussa M, Richard V, NeviereR, Edme JL, Lefebvre P, Staels B. Myocardial contractile dysfunction is associated with impaired mitochondrial function and dynamics in type 2 diabetic but not in obese patients. Circulation 2014;130:554-564.
40. Asburn J, Villareal FJ. The pathogenesis of myocardial fibrosis in the setting of diabetic cardiomyopathy. J Am Coll Cardiol 2006;47:693-700.
41. McGavock JM, Victor RG, Unger RH, Szczepaniak LS. Adiposity of the heart, revisited. Ann Intern Med 2006;144:517-524.
42. Boudina S, Abel ED. Diabetic cardiomyopathy revisited. Circulation 2007;115: 3213-3223.
43. Harmancey R, Taegtmeyer H. The complexities of diabetic cardiomyopathy: lessons from patients and animal models. Curr Diab Rep 2008;8:243-248.
44. Symons JD, Abel ED. Lipotoxicity contributesto endothelial dysfunction: afocus on the contribution from ceramide. Rev Endocr Metab Disord 2013;14:59-68.
45. Bayeva M, Sawicki KT, Ardehali H. Taking diabetes to heart - deregulation of myocardial lipid metabolism in diabetic cardiomyopathy. J Am Heart Assoc 2013;2: e000433.
46. Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963;1:785-789.
47. Herrero P, Peterson LR, McGill JB, Matthew S, Lesniak D, Dence C, Gropler RJ. Increasedmyocardialfattyacidmetabolism inpatientswithtype1diabetesmellitus. J Am Coll Cardiol 2006;47:598-604.
48. Rijzewijk LJ, van der Meer RW, Lamb HJ, de Jong HW, Lubberink M, Romijn JA, Bax JJ, de Roos A, Twisk JW, Heine RJ, Lammertsma AA, Smit JW, Diamant M. Altered myocardial substrate metabolism and decreased diastolic function in nonischemic human diabetic cardiomyopathy: studies with cardiac positron emission tomography and magnetic resonance imaging. J Am Coll Cardiol 2009;54: 1524-1532.
49. González A, Ravassa S, Beaumont J, López B, Díez J. New targets to treat the structural remodeling of the myocardium. J Am Coll Cardiol 2011;58:1833-1843.
50. McGavock JM, Lingvay I, Zib I, Tillery T, Salas N, Unger R, Levine BD, Raskin P, Victor RG, Szczepaniak LS. Cardiac steatosis in diabetes mellitus: a 1H-magnetic resonance spectroscopy study. Circulation 2007;116:1170-1175.
51. RijzewijkLJ, vanderMeerRW, Smit JW, DiamantM, BaxJJ, Hammer S, RomijnJA, de Roos A, Lamb HJ. Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol 2008;52:1793-1799.
52. Perry DK, Hannun YA. The role of ceramide in cell signalling. Biochem Biophys Acta 1998;1436:233-243.
53. Zhang L, Ussher JR, Oka T, Cadete VJ, Wagg C, Lopaschuk GD. Cardiac diacylglycerol accumulation in high fat-fed mice is associated with impaired insulinstimulated glucose oxidation. Cardiovasc Res 2011;89:148-156.
54. ε-(Carboxymethyl)lysine depositions in intramyocardial arteries in human acute myocardial infarction. A predictor or reflection of infarction? Arterioscl Thromb Vasc Biol 2006;26:2497-2503.
55. Anderson MM, Requena JR, Crowley JR, Thorpe SR, Heinecke JW. The myeloperoxidase system of human phagocytes generates N-epsilon-(carboxymethyl)lysine on proteins: a mechanism for producing advanced glycation end products atsites of inflammation. J Clin Invest 1999;104:103-113.
56. Zieman SJ, Melenovsky V, Clattenburg L, Corretti MC, Capriotti A, Gerstenblith G, Kass DA. Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension. J Hypertens 2007;25:577-583.
57. Donaldson C, Taatjes DJ, Zile M, Palmer B, VanBuren P, Spinale F, Maughan D, Von Turkovich M, Bishop N, LeWinter MM. Combined immunoelectron microscopic and computer-assisted image analyses to detect advanced glycation end-products in human myocardium. Histochem Cell Biol 2010;134:23-30.
58. ZhangM, Kho AL, Anilkumar N, ChibberR, PaganoPJ, Shah AM, Cave AC. Glycated proteins stimulate reactive oxygen species production in cardiac myocytes: involvement of Nox2 (gp91phox)-containing NADPH oxidase. Circulation 2006; 113:1235-1243.
59. Little WC, Zile MR, Kitzman DW, Hundley WG, O'Brien TX, Degroof RC. The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. J Card Fail 2005;11: 191-195.
60. Hartog JW, Willemsen S, van Veldhuisen DJ, Posma JL, van Wijk LM, Hummel YM, Hillege HL, Voors AA, for the BENEFICIAL investigators. Effects of alagebrium, an advanced glycation endproduct breaker, on exercise tolerance and cardiac function in patients with chronic heart failure. Eur J Heart Fail 2011;13:899-908.
61. Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med 2007;356: 830-840.
62. Gottumukkala RV, Lv H, Cornivelli L, Wagers AJ, Kwong RY, Bronson R, Stewart GC, Schulze PC, Chutkow W, Wolpert HA, Lee RT, Lipes MA. Myocardial infarction triggers chronic cardiac autoimmunity in type 1 diabetes. Sci Transl Med 2012;4:138ra80.
63. Selvin E, Lazo M, Chen Y, Shen L, Rubin J, McEnvoy JW, Hoogeveen RC, SharrettAR, Ballantyne CM, Coresh J. Diabetes mellitus, prediabetes and incidence of subclinical myocardial damage. Circulation 2014;130:1374-1382.
64. YoungME, McNultyP, TaegtmeyerH. Adaptationand maladaptation of the heartin diabetes: part II: potential mechanisms. Circulation 2002;105:1861-1870.
65. Witteles RM, Fowler MB. Insulin-resistant cardiomyopathy clinical evidence, mechanisms, and treatment options. J Am Coll Cardiol 2008;51:93-102.
66. Winkler G, Lakatos P, Salamon F, Nagy Z, Speer G, Kovacs M, Harmos G, Dworak O, Cseh K. Elevated serum TNF-alpha level as a link between endothelial dysfunction and insulin resistance in normotensive obese patients. Diabet Med 1999;16:207-211.
67. Lukic L, Lalic NM, Rajkovic N, Jotic A, Lalic K, Milicic T, Seferovic JP, Macesic M, Gajovic JS. Hypertension in obese type 2 diabetes patients is associated with increases in insulin resistance and IL-6 cytokine levels: potential targets for an efficient preventive intervention. Int J Environ Res Public Health 2014;11:3586-3598. .
68. Murray AJ, Anderson RE, Watson GC, Radda GK, Clarke K. Uncoupling proteins in human heart. Lancet 2004;364:1786-1888.
69. Boudina S, Abel ED. Mitochondrial uncoupling: a key contributor to reduced cardiac efficiency in diabetes. Physiology 2006;21:250-258.
70. Rider OJ, Francis JM, Ali MK, Holloway C, Pegg T, Robson MD, Tyler D, Byrne J, Clarke K, Neubauer S. Effects of catecholamine stress on diastolic function and myocardial energetics in obesity. Circulation 2012;125:1511-1519.
71. Diamant M, Lamb HJ, Groeneveld Y, Endert EL, Smit JW, Bax JJ, Romijn JA, de Roos A, Radder JK. Diastolic dysfunction is associated with altered myocardial metabolism in asymptomatic normotensive patients with well-controlled type 2 diabetes mellitus. J Am Coll Cardiol 2003;42:328-335.
72. Phan TT, Abozguia K, Nallur Shivu G, Mahadevan G, Ahmed I, Williams L, Dwivedi G, Patel K, Steendijk P, Ashrafian H, Henning A, Frenneaux M. Heart failure with preserved ejection fraction is characterized by dynamic impairment of active relaxation and contraction of the left ventricle on exercise and associated with myocardial energy deficiency. J Am Coll Cardiol 2009;54:402-409.
73. Lawlor MA, Alessi DR. PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? J Cell Sci 2001;114:2903-2910.
74. Krüger M, Babicz K, von Frieling-Salewsky M, Linke WA. Insulin signaling regulates cardiac titin properties in heart development and diabetic cardiomyopathy. J Mol Cell Cardiol 2010;48:910-916.
75. Schnell O, Kirsch CM, Stemplinger J, Haslbeck M, Standl E. Scintigraphic evidence for cardiac sympathetic dysinnervation in long-term IDDM patients with and without ECG-based autonomic neuropathy. Diabetologia 1995;38:1345-1352.
76. Schnell O, Muhr D, Weiss M, Dresel S, Haslbeck M, Standl E. Reduced myocardial 123I-metaiodobenzylguanidine uptakeinnewlydiagnosed IDDM patients. Diabetes 1996;45:801-805.
77. Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, Levine GN, Narula J, Starling RC, Towbin J, Virmani R, American Heart Association, American College of Cardiology, European Society of Cardiology. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation 2007;116:2216-2233.
78. Stritzke J, Markus MR, Duderstadt S, Lieb W, Luchner A, Döring A, Keil U, Hense HW, Schunkert H, MONICA/KORA Investigators. The aging process of the heart: obesity is the main risk factor for left atrial enlargement during aging the MONICA/KORA (monitoring of trends and determinations in cardiovascular disease/cooperative research in the region of Augsburg) study. J Am Coll Cardiol 2009;54:1982-1989.
79. Takeda Y, Sakata Y, Mano T, Ohtani T, Kamimura D, Tamaki S, Omori Y, Tsukamoto Y, Aizawa Y, Komuro I, Yamamoto K. Competing risks of heart failure with preserved ejection fraction in diabetic patients. Eur J Heart Fail 2011; 13:664-669.
80. Borlaug BA, Redfield MM, Melenovsky V, Kane GC, Karon BL, Jacobsen SJ, Rodeheffer RJ. Longitudinal changes in left ventricular stiffness: a community-based study. Circ Heart Fail 2013;6:944-952.
81. Mikkelsen KV, Møller JE, Bie P, Ryde H, Videbaek L, Haghfelt T. Tei index and neurohormonal activation in patients with incident heart failure: serial changes and prognostic value. Eur J Heart Fail 2006;8:599-608.
82. Mottram PM, Leano R, Marwick TH. Usefulness of B-type natriuretic peptide in hypertensive patients with exertional dyspnea and normal left ventricular ejection fraction and correlation with new echocardiographic indexes of systolic and diastolic function. Am J Cardiol 2003;92:1434-1438.
83. Stahrenberg R, Edelmann F, Mende M, Kockskämper A, Düngen HD, Lüers C, Binder L, Herrmann-Lingen C, Gelbrich G, Hasenfuss G, Pieske B, Wachter R. The novel biomarker growth differentiation factor 15 in heart failure with normal ejection fraction. Eur J Heart Fail 2010;12:1309-1316.
84. Shuai XX, Chen YY, Lu YX, Su GH, Wang YH, Zhao HL, Han J. Diagnosis of heart failurewith preserved ejection fraction: which parameters and diagnostic strategies are more valuable? Eur J Heart Fail 2011;13:737-741.
85. Suskin N, McKelvie RS, Burns RJ, Latini R, Pericak D, Probstfield J, Rouleau JL, Sigouin C, Solymoss CB, Tsuyuki R, White M, Yusuf S. Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure. Eur Heart J 2000;21:1368-1375.
86. Authors/Task Force Members, Rydén L, Grant PJ, Anker SD, Berne C, Cosentino F, Danchin N, Deaton C, Escaned J, Hammes HP, Huikuri H, Marre M, Marx N, Mellbin L, Ostergren J, Patrono C, Seferovic P, Uva MS, Taskinen MR, Tendera M, Tuomilehto J, Valensi P, Zamorano JL, ESC Committee for Practice Guidelines (CPG), Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Document Reviewers, De Backer G, Sirnes PA, Ezquerra EA, Avogaro A, Badimon L, Baranova E, Baumgartner H, Betteridge J, Ceriello A, Fagard R, Funck-Brentano C, Gulba DC, Hasdai D, Hoes AW, Kjekshus JK, Knuuti J, Kolh P, Lev E, Mueller C, Neyses L, Nilsson PM, Perk J, Ponikowski P, Reiner Z, Sattar N, Schächinger V, Scheen A, Schirmer H, Strömberg A, Sudzhaeva S, Tamargo JL, Viigimaa M, Vlachopoulos C, Xuereb RG. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J 2013; 34:3035-3087.
87. Franssen C, Paulus WJ. The future diagnosis of heart failure with normal ejection fraction: less imaging, more biomarkers? Eur J Heart Fail 2011;13:1043-1045.
88. Martos R, Baugh J, Ledwidge M, O'Loughlin C, Murphy NF, Conlon C, Patle A, Donnelly SC, McDonald K. Diagnosis of heart failure with preserved ejection fraction: improved accuracy with the use of markers of collagen turnover. Eur J Heart Fail 2009;11:191-197.
89. GonzálezA, LópezB, QuerejetaR, ZubillagaE, EcheverríaT, DíezJ. Filling pressures and collagen metabolism in hypertensive patients with heart failure and normal ejection fraction. Hypertension 2010;55:1418-1424.
90. Collier P, Watson CJ, Voon V, Phelan D, Jan A, Mak G, Martos R, Baugh JA, Ledwidge MT, McDonald KM. Can emerging biomarkers of myocardial remodelling identify asymptomatic hypertensive patients at risk for diastolic dysfunction and diastolic heart failure? Eur J Heart Fail 2011;13:1087-1095.
91. Cleland JG, Tendera M, Adamus J, Freemantle N, Polonski L, Taylor J. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J 2006; 27:2338-2345.
92. Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, Anderson S, Donovan M, Iverson E, Staiger C, Ptaszynska A, I-PRESERVE Investigators. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 2008; 359:2456-2467.
93. Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Harty B, Heitner JF, Kenwood CT, Lewis EF, O'Meara E, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, Yang S, McKinlay SM, TOPCAT Investigators. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 2014;370:1383-1392.
94. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Køber L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Rønnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, McDonagh T, Sechtem U, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P, ESC Committee for Practice Guidelines. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2012;14:803-869.
95. Farasat SM, Bolger DT, Shetty V, Menachery EP, Gerstenblith G, Kasper EK, Najjar SS. Effect of beta-blocker therapy on rehospitalization rates in women versus men with heart failure and preserved ejection fraction. Am J Cardiol 2010; 105:229-234.
96. Peterson LR, Saeed IM, McGill JB, Herrero P, Schechtman KB, Gunawardena R, Recklein CL, Coggan AR, Demoss AJ, Dence CS, Gropler RJ. Sex and type 2 diabetes: obesity-independent effects on left ventricular substrate metabolism and relaxation in humans. Obesity 2012;20:802-810.
97. Hammer S, Snel M, Lamb HJ, Jazet IM, van der Meer RW, Pijl H, Meinders EA, Romijn JA, de Roos A, Smit JW. Prolonged caloric restriction in obese patients with type 2 diabetes mellitus decreases myocardial triglyceride content and improves myocardial function. J Am Coll Cardiol 2008;52:1006-1012.
98. Schrauwen-Hinderling VB, Hesselink MK, Meex R, van der Made S, Schär M, Lamb H, Wildberger JE, Glatz J, Snoep G, Kooi ME, Schrauwen P. Improved ejection fraction after exercise training in obesity is accompanied by reduced cardiac lipid content. J Clin Endocrinol Metab 2010;95:1932-1938.
99. Schrauwen-Hinderling VB, Meex RC, Hesselink MK, van de Weijer T, Leiner T, Schär M, Lamb HJ, Wildberger JE, Glatz JF, Schrauwen P, Kooi ME. Cardiac lipid content is unresponsive to a physical activity training intervention in type 2 diabetic patients, despite improved ejection fraction. Cardiovasc Diabetol 2011;10:47.
100. th Edition, 2008;4:54-61.
101. Tuunanen H, Engblom E, Naum A, Någren K, Hesse B, Airaksinen KE, Nuutila P, Iozzo P, Ukkonen H, Opie LH, Knuuti J. Free fatty acid depletion acutely decreases cardiac work and efficiency in cardiomyopathic heart failure. Circulation 2006;114: 2130-2137.
102. Hare JL, Hordern MD, Leano R, Stanton T, Prins JB, Marwick TH. Application of an exercise intervention on the evolution of diastolic dysfunction in patients with diabetes mellitus: efficacy and effectiveness. Circ Heart Fail 2011;4:441-449.
103. Kitzman DW, BrubakerPH, Morgan TM, StewartKP, Little WC. Exercisetraining in older patients with heart failure and preserved ejection fraction: a randomized, controlled, single-blind trial. Circ Heart Fail 2010;3:659-667.
104. Edelmann F, Gelbrich G, Düngen HD, Fröhling S, Wachter R, Stahrenberg R, Binder L, Töpper A, Lashki DJ, Schwarz S, Herrmann-Lingen C, Löffler M, Hasenfuss G, Halle M, Pieske B. Exercise training improves exercise capacity and diastolic function in patients with heart failure with preserved ejection fraction: results of the Ex-DHF (Exercise training in Diastolic Heart Failure) pilot study. J Am Coll Cardiol 2011;58:1780-1791.
105. Eurich DT, Weir DL, Majumdar SR, Tsuyuki RT, Johnson JA, Tjosvold L, Vanderloo SE, McAlister FA. Comparative safety and effectiveness of metformin in patients with diabetes mellitus and heart failure: systematic review of observational studies involving 34,000 patients. Circ Heart Fail 2013;6:395-402.
106. Van der Meer RW, Rijzewijk LJ, de Jong HWAM, Lamb HJ, Mark Lubberink M, Romijn JA, Bax JJ, de Roos A, Kamp O, Paulus WJ, Heine RJ, Lammertsma AA, Smit JWA, Diamant M. Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus. Circulation 2009;119:2069-2077.
107. Chen WJ, Rijzewijk LJ, van der Meer RW, Heymans MW, van Duinkerken E, Lubberink M, Lammertsma AA, Lamb HJ, de Roos A, Romijn JA, Smit JW, Bax JJ, Bjerre M, Frystyk J, Flyvbjerg A, Diamant M. Association of plasma osteoprotegerin and adiponectin with arterial function, cardiac function and metabolism in asymptomatic type 2 diabetic men. Cardiovasc Diabetol 2011;10:67.
108. Lago RM, Singh PP, Nesto RW. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials. Lancet 2007;370:1129-1136.
109. von Bibra H, Hansen A, Dounis V, Bystedt T, Malmberg K, Ryden L. Augmented metabolic control improves myocardial diastolic function and perfusion in patients with non-insulin dependent diabetes. Heart 2004;90:1483-1484.
110. Jarnert C, Landstedt-HallinL, Malmberg K, MelcherA, OhrvikJ, PerssonH, RydenL. A randomised trial of the impact of strict glycaemic control on myocardial diastolic function and perfusion reserve. A report from the DADD (diabetes mellitus and diastolic dysfunction) study. Eur J Heart Failure 2009;11:39-47.
111. Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I, SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013;369:1317-1326.
112. Weir DL, McAlister FA, Senthilselvan A, Minhas-Sandu JK, Eurich DT. Sitagliptin use in patients with diabetes and heart failure: a population based retrospective cohort study. J Am Coll Cardiol HF 2014;2:573-582.
113. Bhatt DL, Cavender MA. Do dipeptidyl peptidase-4 inhibitors increase the risk of heart failure? J Am Coll Cardiol HF 2014;2:583-585.
114. Folmes CD, Clanachan AS, Lopaschuk GD. Fatty acids attenuate insulin regulation of 5′-AMP-activated protein kinase and insulin cardioprotection after ischemia. Circ Res 2006;99:61-68.
115. Kötter S, Unger A, Hamdani N, Lang P, Vorgerd M, Nagel-Steger L, Linke WA. Human myocytes are protected from titin aggregation-induced stiffening by small heat shock proteins. J Cell Biol 2014;204:187-202.
116. Munaf M, Pellicori P, Allgar V, Wong K. A meta-analysis of the therapeutic effects of glucagon-like peptide-1 agonist in heart failure. Int J Pept 2012;2012:249827.
117. Tahrani AA, Barnett AH, Bailey CJ. SGLT inhibitors in management of diabetes. Lancet Diabetes Endocrinol 2013;1:140-151.
118. Maisch B, Richter A, Koelsch S, Alter P, Funck R, Pankuweit S. Management of patients with suspected (peri-) myocarditis and inflammatory dilated cardiomyopathy. Herz 2006;31:881-890.
119. Shekelle PG, Rich MW, Morton SC, Atkinson CS, Tu W, Maglione M, Rhodes S, Barrett M, Fonarow GC, Greenberg B, Heidenreich PA, Knabel T, Konstam MA, Steimle A, Warner Stevenson L. Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials. J Am Coll Cardiol 2003;41:1529-1538.
120. Martin DT, McNitt S, Nesto RW, Rutter MK, Moss AJ. Cardiac resynchronization therapy reduces the risk of cardiac events in patients with diabetes enrolled in the multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy (MADIT-CRT). Circ Heart Fail 2011;4:332-338.
121. Smooke S, Horwich TB, Fonarow GC. Insulin-treated diabetes is associated with a marked increase in mortality in patients with advanced heart failure. Am Heart J 2005;149:168.
122. Lexis CP, van der Horst IC, Lipsic E, Wieringa WG, de Boer RA, van den Heuvel AF, van der Werf HW, Schurer RA, Pundziute G, Tan ES, Nieuwland W, Willemsen HM, Dorhout B, Molmans BH, van der Horst-Schrivers AN, Wolffenbuttel BH, ter Horst GJ, van Rossum AC, Tijssen JG, Hillege HL, de Smet BJ, van der Harst P, van Veldhuisen DJ, GIPS-III Investigators. Effect of metformin on left ventricular function afteracute myocardialinfarctionin patients without diabetes: the GIPS-III randomized clinical trial. JAMA 2014;311:1526-1535.
123. Read PA, Khan FZ, Heck PM, Hoole SP, Dutka DP. DPP-4 inhibition by sitagliptin improves the myocardial response to dobutamine stress and mitigates stunning in a pilot study of patients with coronary artery disease. Circ Cardiovasc Imaging 2010;3:195-201.